TABLE OF CONTENTS
ABOUT DATAMONITOR HEALTHCARE 2
About the Central Nervous System (CNS) pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Strategic scoping and focus 3
Datamonitor insight into the disease market 3
Contributing experts 5
Related reports 5
CHAPTER 2 MARKET DEFINITION AND OVERVIEW 7
Market definition for this report 7
Current seven major market assessment 8
The seven major multiple sclerosis market grew to over $5.3 billion in 2007 8
US shows lowest yearly growth yet still accounts for over 65% of the seven major markets for multiple sclerosis in 2007 10
Despite strong growth over 2007 the UK remains a small market 11
Rest of the World snapshot 12
Rest of the world multiple sclerosis market is growing faster than the seven major markets 12
Canada is by far the largest emerging multiple sclerosis market 14
No one product dominates the multiple sclerosis market in the rest of the world 15
Future seven major market assessment 17
Comparison with previous forecast 17
Similar market dynamics between the two forecasts with Tysabri's upgrade the most significant change 17
Top-line events driving future market dynamics 18
Three distinct phases will determine the multiple sclerosis market dynamics over the next 10 years 18
Forecast data tables 19
CHAPTER 3 BRAND DYNAMICS 23
Multiple sclerosis competitive landscape 23
Current brand dynamics 23
Biogen Idec's Avonex remains top-selling multiple sclerosis therapy in 2007 23
Copaxone overtakes Avonex in the US in 2007 while Rebif leads in Europe 24
Avonex and Copaxone are more reliant on US sales 25
Tysabri became the sixth available multiple sclerosis therapy following its relaunch in 2006 26
Future market forecast by brand 26
Despite recent safety fears Tysabri is predicted to become a leading brand in the multiple sclerosis market 26
Novartis's FTY720 expected to achieve the greatest sales of all current late-stage pipeline products 28
Marketed brands overview 29
Avonex (interferon beta-1a, Biogen Idec and Genzyme) 29
Overview 29
Ongoing post-marketing studies unlikely to make much of an impact on Avonex prescriptions 31
Avonex sales to decline as Tysabri cannibalizes sales and biosimilar versions and pipeline products come to market 31
Copaxone (glatiramer acetate, Teva and Sanofi-Aventis) 33
Overview 33
Postmarketing trial results provide mixed market opportunities for Copaxone 35
Copaxone sales to decline following patent expiry and increased market competition from pipeline products 38
Rebif (interferon beta-1a, Merck Serono and Pfizer) 40
Overview 40
Merck Serono looks for Rebif to succeed through improved tolerability and early intervention 43
Increased market competition to offset positive near-term growth 45
Betaseron (interferon beta-1b, Bayer Schering) 47
Overview 47
Post-marketing studies provide mixed outlook for future Betaseron market growth 49
Limited future growth for Betaseron as Extavia cannibalizes sales and biosimilar versions and multiple pipeline products come to market 50
Tysabri (natalizumab, Biogen Idec and Elan) 52
Overview 52
Two new confirmed cases of PML rocks initially strong 2008 Tysabri uptake 54
Tysabri's sales forecast upgraded, however long-term growth hinges on the incidence and management of new PML cases 57
Novantrone (mitoxantrone) 60
Reintroduction of Tysabri pushes Novantrone further down the prescribing pathway 60
Key late-stage pipeline overview 62
Extavia (interferon beta-1b, Novartis) 63
Novartis's Extavia added to forecast update 63
US Extavia approval expected to follow May 2008 European approval 63
Establishing a presence in the multiple sclerosis market is of more importance to Novartis than multi-million dollar Extavia sales 64
Mylinax (oral cladribine, Merck Serono and Teva) 66
Overview 66
Phase III study fully enrolled with results expected for early 2009 66
Fast Track status provides oral cladribine with opportunity to become the first oral disease-modifier to market 68
Oral cladribine forecasts downgraded as price is reduced to account for anticipated add-on positioning 68
Fingolimod (FTY720, Novartis and Mitsubishi Tanabe Pharma) 71
Overview 71
Primary Phase III studies fully enrolled with results expected for late 2009 71
Three-year Phase II results show continued low relapse and disease activity 73
Long-term safety of FTY720 remains a concern 73
Extavia launch crucial for Novartis to build a presence in the multiple sclerosis market prior to FTY720 launch 75
Forecast update sees FTY720 uptake plateau off earlier due to greater pipeline competition 75
Panaclar (BG-12, Biogen idec) 77
Overview 77
Phase III studies continue to recruit patients 77
Thrice-daily dosing and anticipated positioning as add-on therapy results in assumed price reduction and downgraded forecast for BG-12 78
Dirucotide (MBP8298, BioMS Medical and Eli Lilly) 81
Overview 81
MBP8298 could become the only approved treatment for true secondary-progressive multiple sclerosis 81
Datamonitor successfully predicted Big Pharma collaboration in previous forecast 83
Forecast upgraded due to increased annual price point and greater recognition of the secondary-progressive market sector potential 84
Laquinimod (Active Biotech and Teva) 86
Overview 86
First Phase III study initiated in September 2007 86
Phase III efficacy profile will dictate laquinimod's positioning as either monotherapy or add-on therapy 87
Laquinimod overtakes teriflunomide to become the penultimate pipeline oral disease modifier to launch in forecast period 88
Campath (alemtuzumab, Genzyme and Bayer Schering) 90
Alemtuzumab added to forecast update 90
Phase II data show superior efficacy compared to Rebif 90
Phase III alemtuzumab clinical program initiated in second half of 2007 92
Alemtuzumab's greatest potential in multiple sclerosis is when given early 93
Side-effect issues will limit alemtuzumab's return from multiple sclerosis 94
Alemtuzumab's yearly price will bode well for reimbursement status but will prevent Genzyme and Bayer generating large revenues in multiple sclerosis 95
Teriflunomide (Sanofi-Aventis) 96
Overview 96
Phase III program broadened to offset slow initial enrollment 97
Teriflunomide forecast downgraded as regulatory submission now anticipated for 2012 and market positioning as add-on appears likely outcome 99
Anti-CD20 monoclonal antibody (Genentech and Biogen idec) 100
Rituxan not forecast to launch for multiple sclerosis 100
Ocrelizumab replaces Rituxan in Datamonitor's multiple sclerosis forecast 101
Biosimilar interferon beta 106
Despite lower costs brand loyalty may limit reward of biosimilars in multiple sclerosis 106
Biferonex (interferon beta-1a) 107
Unforecasted multiple sclerosis pipeline candidates 109
BIBLIOGRAPHY 110
Journal papers and broker reports 110
Websites 110
Datamonitor reports 115
APPENDIX A - MARKET ASSUMPTIONS 116
New product launches 116
Patent expiries 117
Data definitions, limitations and assumptions 117
Standard units 117
Japanese market data 117
Derivation of sales forecasts and pricing trends 118
Forecast methodology 118
APPENDIX B 119
Contributing experts 119
Report methodology 119
About Datamonitor 119
About Datamonitor Healthcare 120
About the central nervous system analysis team 121
Disclaimer 122
List of Tables
Table 1: Comparison of branded drug sales ($m) for multiple sclerosis in the seven major markets (7MM) and the Rest of the World (RoW), 2004-07 15
Table 2: Overview of the top three small and emerging markets for the leading five multiple sclerosis brands by sales ($m), 2007 16
Table 3: Multiple sclerosis-specific sales forecasts for the seven major markets ($m), 2007-2017 20
Table 4: Leading branded drug sales ($m) for multiple sclerosis in the seven major markets, 2004-07 23
Table 5: Branded drug sales ($m) for multiple sclerosis disease-modifying drugs in the seven major markets, 2007-2017 27
Table 6: Forecast for key products in late-stage R&D pipeline for multiple sclerosis, 2008 28
Table 7: Avonex: key facts, 2008 29
Table 8: Avonex (interferon-beta 1a) sales ($m) in each of the seven major markets, 2004-07 30
Table 9: Sales forecast ($m) for Avonex in the seven major markets, 2007-17 33
Table 10: Copaxone: key facts, 2008 34
Table 11: Copaxone (glatiramer acetate) sales ($m) in each of the seven major markets, 2004-07 35
Table 12: Sales forecast ($m) for Copaxone in the seven major markets, 2007-17 40
Table 13: Rebif: key facts, 2008 41
Table 14: Rebif (interferon-beta 1a) sales ($m) in each of the seven major markets, 2004-07 42
Table 15: Sales forecast ($m) for Rebif in the seven major markets, 2007-17 47
Table 16: Betaseron: key facts, 2008 48
Table 17: Betaseron (interferon-beta 1b) sales ($m) in each of the seven major markets, 2004-07 49
Table 18: Sales forecast ($m) for Betaseron in the seven major markets, 2007-17 52
Table 19: Tysabri: key facts, 2008 53
Table 20: Tysabri (natalizumab) sales ($m) in each of the seven major markets, 2004-07 54
Table 21: Sales forecast ($m) for Tysabri in the seven major markets, 2007-17 59
Table 22: Novantrone: key facts, 2008 61
Table 23: Sales forecast ($m) for Extavia in the seven major markets, 2007-17 66
Table 24: Key ongoing oral cladribine multiple sclerosis studies, 2008 67
Table 25: Multiple sclerosis-specific sales forecast ($m) for oral cladribine (Mylinax) in the seven major markets, 2007-17 71
Table 26: Key ongoing FTY720 multiple sclerosis studies, 2008 72
Table 27: Multiple sclerosis-specific sales forecast ($m) for FTY720 (fingolimod) in the seven major markets, 2007-17 77
Table 28: Key ongoing BG-12 multiple sclerosis studies, 2008 78
Table 29: Multiple sclerosis-specific sales forecast ($m) for BG-12 (Panaclar) in the seven major markets, 2007-17 80
Table 30: Key ongoing MBP8298 multiple sclerosis studies, 2008 83
Table 31: Multiple sclerosis-specific sales forecast ($m) for MBP8298 (Dirucotide) in the seven major markets, 2007-17 85
Table 32: Key ongoing laquinimod multiple sclerosis studies, 2008 87
Table 33: Multiple sclerosis-specific sales forecast ($m) for laquinimod in the seven major markets, 2007-17 89
Table 34: Phase II 2-year data for alemtuzumab in multiple sclerosis 91
Table 35: Key ongoing alemtuzumab multiple sclerosis studies, 2008 92
Table 36: Multiple sclerosis-specific sales forecast ($m) for alemtuzumab (Campath) in the seven major markets, 2007-17 96
Table 37: Key ongoing teriflunomide multiple sclerosis studies, 2008 98
Table 38: Multiple sclerosis-specific sales forecast ($m) for teriflunomide in the seven major markets, 2007-17 100
Table 39: Multiple sclerosis-specific sales forecast ($m) for ocrelizumab in the seven major markets, 2007-17 105
Table 40: Sales forecast ($m) for interferon beta biosimilars in the seven major markets, 2007-17 108
Table 41: Unforecasted developmental disease-modifying pipeline drugs in Phase II or higher development for multiple sclerosis, 2008 109
Table 42: Datamonitor's estimated launch dates for multiple sclerosis products in the US, Japan and 5EU, 2008-2017 116
Table 43: Anticipated patent expiry dates for multiple sclerosis brands in the US, Japan and 5EU, 2008-2017 117
List of Figures
Figure 1: Multiple sclerosis market value ($ billion) in the US, 5EU and Japan, 2004-07 9
Figure 2: Multiple sclerosis market sales volume (SU million) in the US, 5EU and Japan, 2004-07 10
Figure 3: Multiple sclerosis-specific sales by country in the seven major markets, 2006-07 11
Figure 4: Multiple sclerosis market sales value ($) and volume (SUs) in the rest of the world, 2004-07 12
Figure 5: Rest of the world versus the US and Japan and 5EU market sales ($m) split in the multiple sclerosis market, 2007 13
Figure 6: Multiple sclerosis market sales value ($m) in the 10 highest value emerging markets, 2004-07 14
Figure 7: Comparison of Datamonitor's updated multiple sclerosis market forecast to 2017 with the previous market forecast to 2016 17
Figure 8: Forecast multiple sclerosis market value ($m) in the seven major markets, 2008-2017 19
Figure 9: Impact of key events on the multiple sclerosis market, 2008-2017 22
Figure 10: Multiple sclerosis market position of the leading four disease-modifying therapies across the seven major markets, 2007 24
Figure 11: Proportion of the leading five multiple sclerosis brand sales value originating from the US, 5EU/Japan combined, and the rest of the world, 2007 25
Figure 12: Timeline: launch dates of disease-modifying therapies for the treatment of multiple sclerosis, 1993-2006 26
Figure 13: Multiple sclerosis-specific sales ($m) forecast for Avonex in the seven major markets, 2007-2017 32
Figure 14: Multiple sclerosis-specific sales ($m) forecast for Copaxone in the seven major markets, 2007-2017 39
Figure 15: REFLEX study and positioning in multiple sclerosis treatment 45
Figure 16: Multiple sclerosis-specific sales ($m) forecast for Rebif in the seven major markets, 2007-2017 46
Figure 17: Multiple sclerosis-specific sales ($m) forecast for Betaseron in the seven major markets, 2007-2017 51
Figure 18: Datamonitor's 2007 and updated sales ($m) forecast for Biogen Idec and Elan's Tysabri in the seven major markets, 2007-2017 58
Figure 19: Comparative sales forecast ($m) of the nine pipeline products launched during Datamonitor's 10-year multiple sclerosis market forecast, 2008-17 62
Figure 20: Multiple sclerosis-specific sales ($m) forecast for Extavia in the seven major markets, 2007-2017 65
Figure 21: Datamonitor's 2007 and updated sales ($m) forecast for Merck Serono's and Teva's oral cladribine (Mylinax) in the seven major markets, 2007-2017 70
Figure 22: Datamonitor's 2007 and updated sales ($m) forecast for Novartis's FTY720 (fingolimod) in the seven major markets, 2007-2017 76
Figure 23: Datamonitor's 2007 and updated sales ($m) forecast for Biogen Idec's BG-12 (Panaclar) in the seven major markets, 2007-2017 80
Figure 24: Datamonitor's 2007 and updated sales ($m) forecast for BioMS and Eli Lilly's MBP8298 (Dirucotide) in the seven major markets, 2007-2017 84
Figure 25: Datamonitor's 2007 and updated sales ($m) forecast for Teva and Active Biotech's laquinimod in the seven major markets, 2007-2017 89
Figure 26: Multiple sclerosis-specific sales ($m) forecast for alemtuzumab (Campath) in the seven major markets, 2007-2017 95
Figure 27: Datamonitor's 2007 and updated sales ($m) forecast for Sanofi-Aventis's teriflunomide in the seven major markets, 2007-2017 99
Figure 28: Datamonitor's 2007 Rituxan and updated ocrelizumab multiple sclerosis-specific sales ($m) forecast for in the seven major markets, 2007-2017 104